ORGANIC LETTERS
Synthesis of Disubstituted [60]Fullerene-Fused Lactones: Ferric Perchlorate-Promoted Reaction of [60]Fullerene with Malonate Esters
2010 Vol. 12, No. 21 4896-4899
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Fa-Bao Li,† Xun You,† and Guan-Wu Wang*,†,‡ Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry, and Department of Chemistry, UniVersity of Science and Technology of China, Hefei, Anhui 230026, P. R. China, and State Key Laboratory of Applied Organic Chemistry, Lanzhou UniVersity, Lanzhou, Gansu 730000, P. R. China
[email protected] Received August 30, 2010
ABSTRACT
The ferric perchlorate-mediated reaction of [60]fullerene with substituted malonate esters in the presence of acetic anhydride afforded the rare disubstituted [60]fullerene-fused lactones. A possible reaction mechanism is proposed.
Although a large variety of reactions for the functionalization of fullerenes have been explored over the past 20 years,1 the metal salt-mediated reactions of [60]fullerene (C60) are relatively underdeveloped. Recently, our group has been interested in reactions of C60 mediated by metal salts such as Mn(OAc)3,2,3 Cu(OAc)2,3c Pb(OAc)4,3h Pd(OAc)2,4 and Fe(ClO4)35 to obtain a variety of novel compounds with desired moieties.
Up to now, only a few papers described the lactonization reactions of C60.3g-i,6,7 Foote et al. reported the synthesis of two C60-fused γ-lactones by the [2 + 2] cycloaddition of C60 with diethylaminopropyne/ketene acetal, subsequent ring opening by acid hydrolysis, and final oxidative cyclization in the presence of charcoal.6 We disclosed the preparation of four C60-fused δ-lactones through the reaction of C60 with anthranilic acids and isoamyl nitrite in the presence of triethylamine.7 We previously revealed the facile one-step reaction of C60 with carboxylic acids, or with carboxylic
†
University of Science and Technology of China. Lanzhou University. (1) For selected reviews, see: (a) Hirsch, A. Synthesis 1995, 895. (b) Thilgen, C.; Diederich, F. Chem. ReV. 2006, 106, 5049. For some recent papers, see: (c) Murata, M.; Maeda, S.; Morinaka, Y.; Murata, Y.; Komatsu, K. J. Am. Chem. Soc. 2008, 130, 15800. (d) Filippone, S.; Maroto, E. E.; Martin-Domenech, A.; Suarez, M.; Martin, N. Nat. Chem. 2009, 1, 578. (e) Clavaguera, S.; Khan, S. I.; Rubin, Y. Org. Lett. 2009, 11, 1389. (f) Wang, G.-W.; Lu, Y.-M.; Chen, Z.-X. Org. Lett. 2009, 11, 1507. (g) Nambo, M.; Wakamiya, A.; Yamaguchi, S.; Itami, K. J. Am. Chem. Soc. 2009, 131, 15112. (h) Matsuo, Y.; Ichiki, T.; Radhakrishnan, S. G.; Guldi, D. M.; Nakamura, E. J. Am. Chem. Soc. 2010, 132, 6342. (i) Zhang, G.; Liu, Y.; Liang, D.; Gan, L.; Li, Y. Angew. Chem., Int. Ed. 2010, 49, 5293. (j) Tzirakis, M. D.; Orfanopoulos, M. Angew. Chem., Int. Ed. 2010, 49, 5891. (2) For a review, see: Wang, G.-W.; Li, F.-B. J. Nanosci. Nanotechnol. 2007, 7, 1162. ‡
10.1021/ol102056k 2010 American Chemical Society Published on Web 09/29/2010
(3) (a) Zhang, T.-H.; Lu, P.; Wang, F.; Wang, G.-W. Org. Biomol. Chem. 2003, 1, 4403. (b) Wang, G.-W.; Zhang, T.-H.; Cheng, X.; Wang, F. Org. Biomol. Chem. 2004, 2, 1160. (c) Wang, G.-W.; Li, F.-B. Org. Biomol. Chem. 2005, 3, 794. (d) Chen, Z.-X.; Wang, G.-W. J. Org. Chem. 2005, 70, 2380. (e) Cheng, X.; Wang, G.-W.; Murata, Y.; Komatsu, K. Chin. Chem. Lett. 2005, 16, 1327. (f) Wang, G.-W.; Yang, H.-T.; Miao, C.-B.; Xu, Y.; Liu, F. Org. Biomol. Chem. 2006, 4, 2595. (g) Wang, G.-W.; Li, F.-B.; Zhang, T.-H. Org. Lett. 2006, 8, 1355. (h) Li, F.-B.; Liu, T.-X.; Huang, Y.-S.; Wang, G.-W. J. Org. Chem. 2009, 74, 7743. (i) Li, F.-B.; Zhu, S.-E.; Wang, G.-W. Chin. Sci. Bull. 2010, 55, 2909. (4) (a) Zhu, B.; Wang, G.-W. J. Org. Chem. 2009, 74, 4426. (b) Zhu, B.; Wang, G.-W. Org. Lett. 2009, 11, 4334. (5) (a) Li, F.-B.; Liu, T.-X.; Wang, G.-W. J. Org. Chem. 2008, 73, 6417. (b) Li, F.-B.; Liu, T.-X.; You, X.; Wang, G.-W. Org. Lett. 2010, 12, 3258. (6) Bernstein, R.; Foote, C. S. Tetrahedron Lett. 1998, 39, 7051. (7) Wang, G.-W.; Zhu, B. Chem. Commun. 2009, 1769.
anhydrides, or with malonic acids in the presence of Mn(OAc)3 to afford three C60-fused γ-lactones.3g Recently, we further extended the Mn(OAc)3-promoted reaction of C60 with various carboxylic acids in the presence of 4-dimethylaminopyridine to afford a series of C60-fused γ-lactone derivatives.3h,i Unfortunately, nearly all of the reported C60fused γ-lactones are monosubstituted lactones. Only one disubstituted C60-fused γ-lactone was reported, and it was formed from the Mn(OAc)3-mediated reaction of C60 with isobutyric acid.3h However, the concurrent formation of a fullerenyl ester byproduct originated from the facile generation of a secondary radical via decarboxylation from isobutyric acid was unavoidable. The isolated yield (17%) of the unsymmetrical fullerenyl ester was even higher than that (10%) of the desired C60-fused γ-lactone under the employed standard conditions.3h It seems that the synthesis of disubstituted C60-fused γ-lactones from carboxylic acids in high yields is quite challenging. This obstacle prompted us to develop an alternative efficient protocol to obtain the scarce disubstituted C60-fused γ-lactones. In continuation of our interest in Fe(ClO4)3-mediated reactions of C60,5 herein we describe the successful synthesis of disubstituted C60-fused γ-lactones through the reaction of C60 with substituted malonate esters in the presence of Fe(ClO4)3 and acetic anhydride. We previously reported that the Mn(OAc)3-mediated reaction of C60 with dialkyl malonates, i.e., CH2(CO2Me)2 and CH2(CO2Et)2, in refluxing chlorobenzene afforded the singly bonded fullerene dimers [(RO2C)2CH]C60C60[CH(CO2R)2] and 1,4-adducts C60[CH(CO2R)2]2, while the corresponding reaction with BrCH(CO2Et)2 generated a 1,4-adduct and a 1,16-adduct of C60.3a In contrast, the Mn(OAc)3-promoted reaction of C60 with substituted malonate esters in refluxing toluene gave the benzyl-substituted unsymmetrical 1,4-adducts of C60.3b In all of the aforementioned reactions, no C60-fused lactones could be identified.3a,b More recently, we attempted the Mn(OAc)3-mediated reaction of C60 with diethyl methylmalonate (1a) in an alternative solvent to avoid the participation of toluene. Interestingly, we obtained disubstituted C60-fused γ-lactone 2a besides 1,4adduct 3a and 1,16-adduct 4a as the major products along with other byproducts from the reaction of C60 with diethyl methylmalonate (1a) and Mn(OAc)3 in a molar ratio of 1:2:2 in o-dichlorobenzene (ODCB) at 140 °C and under nitrogen atmosphere (Scheme 1).8 It should be emphasized that the protection of a nitrogen atmosphere proved to be crucial for the successful synthesis of C60-fused lactone 2a as well as 1,4-adduct 3a and 1,16adduct 4a, with either little or no products being obtained in air. Nevertheless, the poor yield and selectivity for the formation of lactone 2a led us to explore other reaction conditions to selectively obtain the rare disubstituted C60fused lactone. To our great satisfaction, we found that Fe(ClO4)3 in place of Mn(OAc)3 could dramatically improve (8) After we had completed our work, the synthesis of 3a and 4a from the reaction of C602- with diethyl 2-bromo-2-methylmalonate appeared: Kokubo, K.; Arastoo, R. S.; Oshima, T.; Wang, C.-C.; Gao, Y.; Wang, H.-L.; Geng, H.; Chiang, L. Y. J. Org. Chem. 2010, 75, 4574. Org. Lett., Vol. 12, No. 21, 2010
Scheme 1. Mn(OAc)3-Mediated Reaction of C60 with 1a Affording C60-Fused 2a, 1,4-Adduct 3a, and 1,16-Adduct 4a
the selectivity. The reaction conditions were screened for the model reaction of C60 with 1a mediated by Fe(ClO4)3 (Table 1). The reaction of C60 with 1a, Fe(ClO4)3·xH2O
Table 1. Optimization of Reaction Conditions for the Fe(ClO4)3 Reaction of C60 with 1a
reaction reaction yield of recovered entry molar ratioa temp (°C) time (min) 2a (%)b C60 (%) 1 2 3 4 5 6 7 8 9
1:2:2:20 1:2:2:20 1:2:2:20 1:2:2:10 1:2:2:30 1:2:2:20 1:2:2:0 1:2:2:0c,d 1:2:2:20d,e
25 40 60 60 60 80 60 60 60
300 120 20 60 20 20 120 160 10
16 17 26 20 25 34 9 13 20
81 80 58 62 26 38 89 75 42
a Molar ratio refers to C60:1a:FEP:Ac2O. b Isolated yield. c The reaction was conducted by the dissolution of Fe(ClO4)3·xH2O (FEP) in 1a (direct dissolution method). d An unknown product having a polarity similar to C60 was observed besides the desired fullerene lactone. e AcOH was used instead of Ac2O.
(FEP), and Ac2O in a molar ratio of 1:2:2:20 gave lactone 2a in 16% yield at ambient temperature (entry 1, Table 1). Raising the temperature to 60 °C enhanced the yield to 26% (entry 3, Table 1). Increasing or decreasing the amount of Ac2O lowered the product yield (entries 4-5 vs entry 3, Table 1). The isolated yield could be further improved to 34% at the expense of recovered C60 by increasing the reaction temperature to 80 °C (entry 6, Table 1). The absence of Ac2O deteriorated the yield significantly (entries 7-8 vs entry 3, Table 1). Replacing Ac2O with AcOH gave inferior result too (entry 9 vs entry 3, Table 1). The role played by Ac2O is not clear, yet it is known in the literature that Ac2O is beneficial to Fe(ClO4)3-mediated radical reactions.9b Thus, 4897
the molar ratio of 1:2:2:20 for the reagents C60, 1a, Fe(ClO4)3·xH2O, and Ac2O and the reaction temperature of 80 °C were chosen as the optimized reaction conditions. Similar optimized reaction conditions could be successfully extended to the Fe(ClO4)3-mediated reaction of C60 with other substituted malonate esters such as diethyl ethylmalonate (1b), diethyl benzylmalonate (1c), diethyl phenylmalonate (1d), diethyl bromomalonate (1e), and triethyl methanetricarboxylate (1f). Table 2 lists the reaction conditions and
Table 2. Reaction Temperatures, Molar Ratios, Reaction Times, and Yields of C60-Fused Lactones 2a-fa
presence of Ac2O to produce lactone 2e with the retention of the bromo substituent. Ethoxycarbonyl-substituted malonate ester 1f was the least reactive among the investigated substituted malonate esters and required a higher reaction temperature (110 °C). It is noteworthy that acetic anhydride played a crucial role for the successful synthesis of C60-fused lactones, with low and/or poor selectivity being obtained in its absence. Surprisingly, the Fe(ClO4)3-mediated reaction of C60 with diethyl malonate, the unsubstituted malonate ester, at 80 °C for 7 min failed to give the desired C60-fused lactone, instead affording at least four unidentified products. The structures of disubstituted C60-fused lactones 2a-f were fully characterized by HRMS, 1H NMR, 13C NMR, FTIR, and UV-vis spectra. In the 1H NMR spectra of lactones 2a-f, the two methylene protons in the ethoxy group were nonequivalent and split as two double quartets due to the adjacent chiral center. In their 13C NMR spectra, the chemical shifts for the lactone and ester carbons appeared at 166.49-173.56 and 162.91-169.69 ppm, and the two sp3carbons of the C60 skeleton were located at 95.57-96.43 and 68.41-72.40 ppm, close to those of reported C60-fused lactone derivatives in the previous literature.3g-i,6,7 There were at least 46 peaks in the 134-152 ppm region for the 58 sp2-carbons of the C60 moiety for lactones 2a-e, consistent with the C1 symmetry of their molecular structures. In contrast, only 26 lines in the 136-149 ppm region could be found for lactone 2f, agreeing well with its Cs symmetry. The IR spectra of 2a-f showed absorptions at 1786-1798 and 1730-1760 cm-1 due to the lactone and ester groups. Their UV-vis spectra exhibited a peak at 415-419 nm, which is a characteristic absorption for the 1,2-adducts of C60 with the oxygen atom directly attached to the fullerene skeleton.3g-i,6,7 Even though the exact pathway is not quite clear for the formation of disubstituted C60-fused lactones 2, a possible reaction mechanism is proposed and shown in Scheme 2.
a All reactions were carried out with a molar ratio of C60:1:Fe(ClO4)3·xH2O: Ac2O ) 1:2:2:20 in o-dichlorobenzene under nitrogen atmosphere unless indicated otherwise. b Isolated yield; that in parentheses was based on consumed C60. c C60:1d:Fe(ClO4)3·xH2O:Ac2O ) 1:2:2:50.
Scheme 2. Proposed Reaction Mechanism for the Formation of Lactones 2
yields for the Fe(ClO4)3-mediated reaction of C60 with malonate esters 1a-f in the presence of Ac2O, affording the scarce disubstituted C60-fused lactones 2a-f. It should be pointed out that no 1,4-adduct, 1,16-adduct, and singlebonded dimeric adduct of C60 could be identified from these reactions under our optimized conditions. As can be seen from Table 2, all examined malonate esters 1a-f could be utilized to prepare disubstituted C60-fused lactones 2a-f in 12-37% yields (53-71% based on consumed C60). Alkyl-substituted malonate esters 1a-c at 80 °C afforded good isolated yields (27-37%) for monoadducts 2a-c. Interestingly, phenyl-substituted malonate ester 1d was very reactive (reaction temperature at 0 °C) yet gave lower yield due to its tendency to form some byproducts. Diethyl bromomalonate, which has been widely used in the Bingel reaction, could react with C60 and Fe(ClO4)3 in the
Substituted malonate ester reacts with Fe(ClO4)3 to generate radical A accompanied with the formation of Fe(ClO4)2 and HClO4.9 Addition of radical A to C60 produces fullerenyl
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radical B, which undergoes intramolecular cyclization to give radical C. Oxidation of radical C by another molecule of Fe(ClO4)3 leads to cation D along with counteranion ClO4and Fe(ClO4)2. The addition of H2O, originated from hydrated water in Fe(ClO4)3·xH2O or concomitant water in the system, to cation D with the loss of H+ results in E. Elimination of EtOH from intermediate E catalyzed by H+ affords C60-fused lactone 2. The failure to obtain the expected C60-fused lactone from the reaction with diethyl malonate might be due to undesired pathways such as the deprotonation of intermediate cation D and hydrogen atom abstraction from E by the ferric ion. In summary, the reaction of C60 with a substituted malonate ester promoted by Mn(OAc)3 afforded only a small amount of the desired disubstituted C60-fused lactone along with the 1,4- and 1,16-adducts bearing two malonyl groups as the major products. However, the scarce disubstituted C60-fused lactones could be selectively synthesized by simply changing the promoter from Mn(OAc)3 to Fe(ClO4)3, indicating that Fe(ClO4)3 altered the reaction pathway in favor of the formation of the C60-
fused lactones. The synthesized disubstituted C60-fused lactones have lactone and ester moieties, which can be further manipulated to make other fullerene derivatives including hydrofullerenes, fullerene hemiacetals, fullerene hemiketals, and fullerenols.3g,10 A plausible reaction mechanism for the formation of lactones 2 is proposed. The present study hints that the metal salts have significant effects on the outcome of the reactions of C60, and it is worthwhile to further explore their application in fullerene chemistry and organic synthesis in general.
(9) (a) Citterio, A.; Sebastiano, R.; Marion, A.; Santi, R. J. Org. Chem. 1991, 56, 5328. (b) Citterio, A.; Sebastiano, R.; Carvayal, M. C. J. Org. Chem. 1991, 56, 5335.
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Acknowledgment. The authors are grateful for the financial support from the National Natural Science Foundation of China (No. 20972145), the Specialized Research Fund for the Doctoral Program of Higher Education (No. 200803580019), and the National Basic Research Program of China (2006CB922003). Supporting Information Available: Experimental procedures, spectral data, and NMR spectra of 2a-f, 3a, and 4a. This material is available free of charge via the Internet at http://pubs.acs.org.
(10) Wang, G.-W.; Li, F.-B.; Xu, Y. J. Org. Chem. 2007, 72, 4774.
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